The goals of the work are to develop methods and apply them to understand how ribosomes translate the genetic code into amino acid sequences. Many aspects of ribosomal functions are mysterious, such as how fidelity of translation is achieved and how translocation along a messenger RNA maintains the exact 3-base reading frame. GTP-binding proteins, termed elongation factors (EFs), utilize cellular energy to achieve this performance in an unknown way. The current research will elucidate these and other aspects of ribosomal function by novel real- time single-molecule structural biophysics. Protein translation is a ubiquitous function in cell biology and it serves as a prototypical cellular machine transferring information and transducing energy. The functions of EFs also bear directly on other G-proteins, such the proto- oncogene Ras, the visual transducer, transducin, beta-adrenergic signalling, and ATPase motor proteins, such as myosin and kinesin. These proteins all share a common fold and many functional similarities. Thus this fundamental research has very broad impact in biomedicine.